This invention relates to the chloromethylation of deactivated aromatic compounds, more particularly to aromatic compounds substituted with alkyl groups and deactivating substituents.
The chloromethylation of aromatic compounds is a well-known reaction. It is well-known that the result of a chloromethylation reaction depends greatly on the nature of the chloromethylating agent, the catalyst, and the process conditions. Effective chloromethylating agents are formaldehyde, paraformaldehyde or trioxymethylene with hydrogen chloride, and monochloromethyl and .alpha.,.alpha.'-bischloromethyl ethers. The reaction is carried out in the presence of zinc chloride, stannous chloride, stannic chloride, aluminum trichloride, boron trifluoride, ferric chloride, titanium tetrachloride, as well as protic acids --HCL (taken in excess and behaving simultaneously as a reactant), H.sub.2 SO.sub.4, H.sub.3 PO.sub.4, ClSO.sub.3 H and CH.sub.3 COOH. Zinc chloride is used most frequently. To increase its activity ,it is often used with a small amount of aluminum chloride. The chloromethylation of unsubstituted aromatics and alkyl-substituted aromatics is relatively straightforward using the above-described chloromethylation agents and catalysts.
The chloromethylation of aromatic compounds with deactivating substituents requires relatively severe reaction conditions. The chloromethylation of deactivated aromatic compounds can be performed by treatment with formaldehyde and HCl in concentrated sulfuric acid. Specific difficulties arise in the chloromethylation of alkylaryl ketones. In the absence of activating substituents in the benzene ring, the alpha position in the side chain is substituted. The reported cases of chloromethylation of aromatic carboxylic acids, and their esters, have been carried out either in concentrated sulfuric acid solutions or in the presence of substantial amounts of zinc chloride catalyst. Nitrobenzene is not easily chloromethylated. It has been found that nitrobenzene can be chloromethylated using paraformaldehyde and hydrogen chloride in concentrated sulfuric acid at 90.degree. C. to 100.degree. C. Nitrotoluene has been chloromethylated with nearly a quantitative yield in 24 hours using di(chloromethyl)ether with chlorosulfonic acid, or oleum, at temperatures below 10.degree. C. By carrying out this reaction at 40.degree. C. to 50.degree. C. with a large excess of di(chloromethyl)ether in the presence of a larger amount of chlorosulfonic acid or 20 percent oleum, bis-chloromethylated product can be obtained.
Chloromethyl ethers such as bischloromethyl ether and monochloromethyl ether have been used to chloromethylate deactivated aromatics. Usually such deactivated compounds are acted upon by chloromethyl ethers in sulfuric acid or oleum, sometimes in the presence of chlorosulfonic acid.
As described hereinbefore, heretofore known processes for the chloromethylation of deactivated aromatic compounds require the use of relatively harsh conditions and large amounts of protic acids. Furthermore, large amounts of catalysts are normally used for these reactions. Many of the processes use the very reactive and highly toxic bischloromethyl ether. The use of highly active catalysts often results in the formation of unwanted by-products such as diarylmethane derivatives.
What is needed is a process for the chloromethylation of aromatic compounds substituted with deactivating substituents wherein addition of protic mineral acids are not required, relatively mild conditions can be used, less toxic reagents are used, and relatively low by-product formation is experienced.